Claude Nahmias

Course of illness, hippocampal function, and hippocampal volume in major depression

Studies have examined hippocampal function and volume in depressed subjects, but none have systematically compared never-treated first-episode patients with those who have had multiple episodes. We sought to compare hippocampal function, as assessed by performance on hippocampal-dependent recollection memory tests, and hippocampal volumes, as measured in a 1.5-T magnetic resonance imager, in depressed subjects experiencing a postpubertal onset of depression. Twenty never-treated depressed subjects in a first episode of depression were compared with matched healthy control subjects. Seventeen depressed subjects with multiple past episodes of depression were also compared with matched healthy controls and to the first-episode patients. Both first- and multiple-episode depressed groups had hippocampal dysfunction apparent on several tests of recollection memory; only depressed subjects with multiple depressive episodes had hippocampal volume reductions. Curve-fitting analysis revealed a significant logarithmic association between illness duration and hippocampal volume. Reductions in hippocampal volume may not antedate illness onset, but volume may decrease at the greatest rate in the early years after illness onset.

Slower progression of Parkinson's disease with ropinirole versus levodopa: The REAL-PET study

Preclinical studies suggest ropinirole (a D2/D3 dopamine agonist) may be neuroprotective in Parkinsons disease (PD), and a pilot clinical study using 18F‐dopa positron emission tomography (PET) suggested a slower loss of striatal dopamine storage with ropinirole compared with levodopa. This prospective, 2‐year, randomized, double‐blind, multinational study compared the rates of loss of dopamine‐terminal function in de novo patients with clinical and 18F‐dopa PET evidence of early PD, randomized 1 to 1 to receive either ropinirole or levodopa. The primary outcome measure was reduction in putamen 18F‐dopa uptake (Ki) between baseline and 2‐year PET. Of 186, 162 randomized patients were eligible for analysis. A blinded, central, region‐of‐interest analysis showed a significantly lower reduction (p = 0.022) in putamen Ki over 2 years with ropinirole (−13.4%; n = 68) compared with levodopa (−20.3%; n = 59; 95% confidence interval [CI], 0.65–13.06). Statistical parametric mapping localized lesser reductions in 18F‐dopa uptake in the putamen and substantia nigra with ropinirole. The greatest Ki decrease in each group was in the putamen (ropinirole, −14.1%; levodopa, −22.9%; 95% CI, 4.24–13.3), but the decrease was significantly lower with ropinirole compared with levodopa (p < 0.001). Ropinirole is associated with slower progression of PD than levodopa as assessed by 18F‐dopa PET. Ann Neurol 2003

Striatal dopamine distribution in Parkinsonian patients during life

Eleven neuropsychologically normal Parkinsonian patients were studied with [18F]6-fluoro-L-dopa and positron tomography. In all of the patients dopaminergic activity was reduced in the putamen on the side opposite to the major motor signs. The reduction was similar in tremulous and rigid patients. In contrast dopaminergic activity was normal in the caudate nuclei. It is argued that the putamen is mainly involved in the regulation of movement while the caudate nuclei assume a role in cognitive processes.

Increased frontal and reduced parietal glucose metabolism in acute untreated schizophrenia

Frontal and parietal lobe metabolism was measured by [18F] fluorodeoxyglucose positron emission tomography in 8 never-medicated DSM-III schizophrenic patients and in 10 control subjects. Patients were in a psychotic episode at the time of this scan. Seven of eight had been ill less than 2 years and had only mild neurocognitive impairment. Frontal lobe glucose metabolism was significantly greater in schizophrenic patients than in controls. This finding differs from that of hypofrontality reported in chronic patients previously treated with neuroleptics. Relative glucose metabolism in the interior parietal lobe was significantly lower in schizophrenic patients than in controls. The frontal/parietal ratios were significantly greater in patients than in controls.

Cerebral Metabolism of 6–[18F]Fluoro‐l‐3,4‐Dihydroxyphenylalanine in the Primate

Abstract: The tracers 6‐[18F]fluoro‐1‐3,4‐dihydroxyphenyl‐alanine (6–[18F]fluoro‐l‐DOPA) and 1‐[14C]DOPA were injected simultaneously into rhesus monkeys, and the time course of their metabolites was measured in the striatum and in the occipital and frontal cortices. In the striatum, 6‐[18F]fluoro‐L‐DOPA was metabolized to 6–[18F]fluorodo‐pamine, 3,4‐dihydroxy‐6–[18F]fluorophenylaceticacid, and 6–[18F]fluorohomovanillic acid. The metabolite pattern was qualitatively similar to that of 1‐[14C]DOPA. 6–[18F]Fluorodopamine was synthesized faster than [14C]do‐pamine. In the frontal cortex, the major metabolite was also 6–[18F]fluorodopamine or [14C]dopamine. In the occipital cortex, the major metabolite was 3‐O‐methyl‐6–[18F]fluoro‐L‐DOPA. On the basis of these data, the images obtained with 6–[l8F]fluoro‐l‐DOPA and positron emission tomography in humans can now be interpreted in neurochemical terms.

The Effects of β1-Blockade on Oxidative Metabolism and the Metabolic Cost of Ventricular Work in Patients With Left Ventricular Dysfunction A Double-Blind, Placebo-Controlled, Positron-Emission Tomography Study

Background—The mechanism for the beneficial effect of β-blocker therapy in patients with left ventricular (LV) dysfunction is unclear, but it may relate to an energy-sparing effect that results in improved cardiac efficiency. C-11 acetate kinetics, measured using positron-emission tomography (PET), are a proven noninvasive marker of oxidative metabolism and myocardial oxygen consumption (MVo2). This approach can be used to measure the work-metabolic index, which is a noninvasive estimate of cardiac efficiency. Methods and Results—The aim of this study was to determine the effect of metoprolol on oxidative metabolism and the work-metabolic index in patients with LV dysfunction. Forty patients (29 with ischemic and 11 with nonischemic heart disease; LV ejection fraction <40%) were randomized to receive metoprolol or placebo in a treatment protocol of titration plus 3 months of stable therapy. Seven patients were not included in analysis because of withdrawal from the study, incomplete follow-up, or nonanal...

Central dopaminergic pathways in hemiparkinsonism examined by positron emission tomography.

[18F]6-fluoro-L-dopa and positron emission tomography has been used to study intracerebral dopamine distribution in five control subjects and six patients with hemiparkinsonism. In the control subjects striatal, frontal and cingulate accumulations were clearly seen. In addition 18F concentrated in the region of the insula and the parietal lobe. In the patients striatal accumulation 18F was reduced in the contralateral striatum, especially in the putamen. The uniformity of distribution of 18F in the striatum on the side of the parkinsonian signs was also irregular. This finding is consonant with the suggestion that intracerebral compensatory mechanisms prevent the manifestation of intracerebral dopamine deficiency from becoming obvious until a late stage of the disease.

ATTENUATION CORRECTION IN PET USING SINGLE PHOTON TRANSMISSION MEASUREMENT

The use of single photon transmission measurement with a rotating rod source has been evaluated to measure the attenuation correction factors in positron emission tomography (PET). The singles projections are resampled into the coincidence geometry using the detector positions and the rod source location. A nonparalyzable dead time correction algorithm was developed for the block detectors used in the McMaster PET scanner. This enables accurate attenuation correction factors (ACFs) to be computed using a wide range of source strengths for transmission scanning. Transaxial resolution is approximately 6 mm, which is comparable to emission scanning performance. Axial resolution is about 25 mm, with only crude source collimation. ACFs are underestimated by as much as 10% due to increased cross-plane scatter, compared to coincidence transmission accuracy. The response of the correction factors to object density is within 15%, when comparing singles transmission measurement to current coincidence transmission measurement. The major advantage of using singles transmission measurement is a dramatically increased count rate. A factor of 7 increase in count rate over coincidence scanning is possible with a 2-mCi transmission rod source. Uniformity of 2% in the transmission images is possible with this source strength and a 2-min acquisition. There are no randoms counted in singles transmission scans, which makes the measured count rate vary linearly with source activity. Singles detector dead time losses are approximately 6% in the detectors opposite a 2-mCi rod source.

Positron emission tomography in the investigation of pediatric inflammatory bowel disease

Background: Endoscopic and radiologic studies are frequently required in inflammatory bowel disease (IBD) to determine disease activity, extent of disease, and delineating disease type. Positron emission tomography (PET) using fluorine‐18‐fluoro‐deoxyglucose to identify metabolically active tissues may offer a simple noninvasive alternative to conventional studies in identification and localization of active intestinal inflammation in children with IBD. The aim of this study was to assess the value of PET in identifying active intestinal inflammation compared with conventional endoscopic and radiologic studies, including small bowel follow‐through and colonoscopy. Methods: Sixty‐five children were enrolled in the study. This included 55 children (mean age, 13.3 yr; range, 7‐18 yr; 20 girls) with newly diagnosed IBD (37) or symptoms suggestive of recurrent disease (18) and 10 children with recurrent abdominal pain (mean age, 12.7 yr; range, 8‐15 yr; 7 girls) who were studied with PET, and the results were compared with small bowel follow‐through with pneumocolon and/or colonoscopy. Thirty‐eight patients had Crohns disease (17 ileal, 12 ileocolic, 5 pancolonic, 3 left‐sided disease, 1 right‐sided disease), and 17 had ulcerative colitis (15 pan‐colitis, 2 left‐sided colitis). Mean time interval between PET and other studies was 30 ± 17.6 days. Results: PET correctly identified active inflammatory disease in 80% of children with IBD (81.5% with Crohns disease; 76.4% with ulcerative colitis) and correctly showed no evidence of inflammation in children with recurrent abdominal pain. Gluorine‐18‐fluoro‐deoxyglucose accumulated at sites that corresponded with active disease at colonoscopy in 83.8% of patients and with small bowel follow‐through with pneumocolon 75.0% of the time. Conclusion: This study suggests that PET offers a noninvasive tool for identifying and localizing active intestinal inflammation in children with IBD. PET may not be able to replace conventional studies; however, it may be useful when conventional studies cannot be performed or fail to be completed.

Striatal dopamine metabolism in living monkeys examined by positron emission tomography.

Positron emission tomography, using the dopa analogue [18F]6-fluoro-L-dopa, has been used to depict the neostriatum in living monkeys. The amount of 18F that accumulated preferentially in the striatum could be augmented by a peripheral decarboxylase inhibitor. Striatal 18F could also be discharged with reserpine. This is the first time that the regional distribution of a neurotransmitter has been demonstrated in monkeys.